重视补体活化在肾小球疾病免疫损伤中的作用

Complement activation in immune injury of glomerular diseases

补体活化在肾小球肾炎中的致病性作用早已得到证实。近年来随着免疫学的进展,对补体异常活化和调节蛋白的异常在部分肾脏病中的作用有了新的认识。研究发现膜增生性肾小球肾炎(MPGN)和C3肾炎主要涉及补体C3转换酶的异常活化、构成以及调节C3转化酶的各种因子的基因突变和自身抗体,甚至多种原因并存均可造成循环补体C3的持续裂解而致病;不典型溶血尿毒综合征(aHUS)则因血管内皮细胞表面补体活化调节异常致病;抗中性粒细胞胞浆抗体(ANCA)相关小血管炎存在着补体旁路途径异常活化,其中补体活化产物C5a可能发挥了重要作用。狼疮肾炎和抗肾小球基底膜(GBM)病,补体旁路途径的活化也与病情活动密切相关。随着对补体异常活化的病理生理机制的了解,以补体成分作为干预靶点的治疗措施也会应运而生。

The pathogenic role of complement activation in glomerulonephritis has been demonstrated decades ago. In recent years, understandings about the roles of abnormal complement activation and regulatory proteins aberration in some kidney diseases have been updated with the rapid progress in immunology. It has been shown by studies that membranoproliferative glomerulonephritis （MPGN） and C3 nephritis were mainly related to abnormal activation of C3 convertase, gene mutations of and autoantibodies against its components and regulatory proteins, or continuous cleavage of circulating C3 complement caused by a variety of reasons. Atypical hemolytic uremic syndrome （aHUS） was caused by dysregulation of complement activation on endothelial surface of blood vessels. Recent studies demonstrated that abnormal complement activation via alternative pathway is an important mechanism for the development of anti-neutrophil cytoplasmic antibody （ANCA） associated system vasculitis in which complement activation product CSa might play an important role. Complement activation via alternative pathway was also associated with disease activity in lupus nephritis and anti-glomerular basement membrane （GBM） disease. With the understanding of the pathophysiological mechanisms of abnormal activation of the complement in these kidney diseases, novel therapies targetting the complement components for intervention will emerge in the ~ture.